Resveratrol mitigates NSAIDs-induced intestinal injury in rats exposed to high altitude hypoxia by reducing the expression levels of Ang- II

Abstract Objective The study aimed to investigate the protective effects of resveratrol against NSAIDs drug-related intestinal injury in rats by regulating the expression of Ang II, as well as mitigating oxidative stress and inflammatory reactions in the intestinal mucosa. Method 60 male Sprague-Dawley rats were randomly assigned to five groups. The control group received a daily gavage of saline (1 ml/100 g/d) in a standard plain-air environment. The rest were housed in a hypoxic chamber, and gavage aspirin at a dosage of 200 mg/kg daily was used to induce NSAID-related intestinal injury in rats. The resveratrol intervention group received resveratrol at varying doses (25, 50, and 100 mg/kg) 2 hours post-aspirin gavage for 3 weeks. Behaving activities, macroscopic appearance, and histological injury of the small intestinal mucosa were assessed and scored in each group. Oxidative stress indicators MPO and SOD, along with inflammatory factors IL-1β, IL-10, and TNF-α, were quantified using ELISA. Immunohistochemistry was employed to detect the expressions of Ang II and ICAM-1 in small intestinal tissues, and their correlation with the degree of intestinal pathology was analysed. Result The small intestine mucosa of rats in the PC group did not show significant macroscopic or pathological injury, whereas other groups exhibited varying degrees of damage. The overall morphology and pathological damage scores were significantly higher than those in the PC group rats (P < 0.05). In comparison with the HN group, intervention with resveratrol led to a reduction in the overall morphology and histopathological injury score of rats (P < 0.05). (1)ELISA test results indicated that, in contrast to the PC group, levels of MPO, SOD, IL-1β, and TNF-α were increased in the HC group rats, while IL-10 levels were notably reduced (P < 0.01). Similarly, compared to the HC group, levels of IL-1β and TNF-α in the HN group rats were elevated, with decreased IL-10 levels (P < 0.05). The resveratrol intervention group rats exhibited significantly lower levels of IL-1 β and TNF-α than the HN group rats (P < 0.01), alongside higher levels of IL-10 (P < 0.05). Notably, the most difference was observed in the medium-dose resveratrol group. (2)Immunohistochemical results revealed a significant increase in Ang II levels in both the HC group and HN group rats (P < 0.05), with ICAM-1 levels significantly elevated in the HN group rats (P < 0.05). (3)The expression of Ang II and ICAM-1 correlates positively with the histological injury to the small intestine mucosa. Following intervention with resveratrol, the expression of Ang II and ICAM-1 was notably lower than that in the HN group rats (P < 0.05). Conclusion Resveratrol can effectively mitigate intestinal injury induced by NSAIDs in a high-altitude environment. The mechanism may involve downregulating the expression of Ang Ⅱ and ICAM-1, alleviating oxidative stress and the inflammatory response of the intestinal mucosa, and preserving intestinal barrier function.